dbSNP rs1395558976: USP51:p.Ser167Phe (chrX-55488440-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_201286.4(USP51):c.500C>T(p.Ser167Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,300 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

USP51
NM_201286.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0480

Publications

0 publications found

Variant links:

Genes affected

USP51 (HGNC:23086): (ubiquitin specific peptidase 51) Enables chromatin binding activity; histone binding activity; and thiol-dependent deubiquitinase. Involved in histone deubiquitination; regulation of cell cycle process; and regulation of double-strand break repair. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

USP51 links:

ENSG00000288739 (HGNC:):

ENSG00000288739 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06566733).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201286.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP51	NM_201286.4	MANE Select	c.500C>T	p.Ser167Phe	missense	Exon 3 of 3	NP_958443.1	Q70EK9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
USP51	ENST00000500968.4	TSL:1 MANE Select	c.500C>T	p.Ser167Phe	missense	Exon 3 of 3	ENSP00000423333.2	Q70EK9
USP51	ENST00000586165.1	TSL:1	c.123+254C>T		intron	N/A	ENSP00000490435.1	A0A1B0GVA6
USP51	ENST00000933765.1		c.500C>T	p.Ser167Phe	missense	Exon 2 of 2	ENSP00000603824.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000558

AC:

AN:

179227

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000126

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1097300

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362722

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26394

American (AMR)

AF:

0.00

AC:

AN:

35151

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19371

East Asian (EAS)

AF:

0.00

AC:

AN:

30180

South Asian (SAS)

AF:

0.00

AC:

AN:

53875

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40392

Middle Eastern (MID)

AF:

0.000484

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841748

Other (OTH)

AF:

0.00

AC:

AN:

46053

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-1.0

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.026

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.44

M_CAP

Benign

0.013

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

PhyloP100

0.048

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.72

REVEL

Benign

0.014

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0070

Polyphen

0.0

Vest4

0.078

MutPred

0.20

Loss of phosphorylation at S167 (P = 0.0116)

MVP

0.043

MPC

0.72

ClinPred

0.027

GERP RS

0.74

PromoterAI

-0.0054

Neutral

(source)

Varity_R

0.098

gMVP

0.21

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over